Nonspecfic or postjunctional supersensitivity is a manifestation of the internal adjustment which excitable cells make to compensate for chronic changes in the level of stimulus they receive via their innervation. Work in this project has established that, in the guinea-pig vas deferens, changes in resting membrane potential, chages in calcium binding or movement and improved electrical coupling all may contribute to postjunctional sensitivity changes. Work in the coming year will be directed toward (1) further analysis of the electrophysiologic, ionic and morphologic changes in the vas deferens, (2) determining the relative importance of each of these changes in the vas deferens and (3) extensonof our investigations to vascular smooth muscle. Measurements to be made include membrane potential, electronic space constant, characteristics of spontaneous and evoked electrical potential, content and uptake of calcium in subcellular fractions, incidence of nexuses in electronmicrographs and dose-response curves with various agonists after induction of supersensitivity by denervation, decentralization or chronic administration of reserpine. BIBLIOGRAPHIC REFERENCES: Lee, T. J-F., D.P. Westfall and W.W. Fleming (1975). The correlation between spontaneous contractions and postjunctional supersensitivity of the smooth muscle of the rat vas deferens. J. Pharmacol. Exp. Ther. 192:136-148. Fleming, W.W. and D.P. Westfall (1975). Altered resting membrane potential in the supersensitive vas deferens of the guinea pig. J. Pharmacol. Exp. Ther. 192:381-389.